Can drug release rate from implants be tailored using poly(urethane) mixtures?

Hydrophobic and hydrophilic thermoplastic poly(urethane) (TPU) mixtures offer the opportunity to tune water swelling capacity and diffusion rate for drugs exhibiting broadly different properties. We sought to (1) assess the range of drug diffusion rates achieved by varying hydrophilic-to-hydrophobic TPU ratio relative to varying ethylene vinyl acetate (EVA) crystallinity; (2) investigate the effect of mixture ratio on permeability of emtricitabine; and (3) investigate the impact of the extrusion process on mixing of the two TPUs and the resulting impact on drug diffusion. The permeability of water-soluble emtricitabine exhibited a 736-fold range across the blends of TPU, but only a 3.4-fold range across the EVA grades investigated. Varying hydrophilic content of the TPU mixture from 0% to 25% (w/w) led to a negligible permeability change, while changing hydrophilic content from 55% to 100% resulted in a linear 3-fold increase in drug permeability. Interestingly, an 123-fold permeability change occurred between 50% and 55% hydrophilic polymer. Extrusion process parameters exhibited minimal impact on homogeneity and drug diffusion. These findings suggest that hydrophilic polymer domains form a continuous network at levels above 55% hydrophilic TPU, thus facilitating a water-filled porous network when exposed to water that provides a mechanism for accelerated drug diffusion.